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蛋白琥珀酸铁用于治疗妇产科的缺铁性贫血
Bracchitta R. & Santoni G.
意大利,米兰 Predabissi 医院,妇产科
Boll. Chim. Farm., Suppl: Clinica e. Terapia. Anno 127, No., 3, 3/1998
简介
40例患有缺铁性贫血的妇产科病人,随机性地使用蛋白琥珀酸铁或铁蛋白作治疗,
每天剂量为80毫克三价铁,疗程为40天.
两种药物都对血液参数有所提升,但蛋白琥珀酸铁的效果比较好,尤其是血清血红
蛋白浓度,红血球数量及在治疗脸色苍白及易疲性方面.
其中一例,服用铁蛋白的病人因产生严重胃肠副作用要退出此测试;而服用蛋白琥
珀酸铁组,只有一个病例产生轻微腹泻.
所有病例耐受性都很好.
介绍
铁是血红蛋白合成的必要元素.
人体内持续性的铁储存量减少会产生相对性至绝对性贫血,缺铁性贫血可因发育时
在饮食吸收率不足或肠胃疾病而产生.
女性经常因月经过多,流产或生育产生慢性出血而引至缺铁性贫血.饮食中的铁质
不足以满足体内需求.
一般在体内,铁质不会被消耗而只会在内质网小胞体被循环作造血系统之用,所以
缺铁一般是因铁流失量超于吸收量所致.
缺铁性贫血是最普遍的贫血,在育龄女性发生率为20-30%,在孕妇发生率为15-58%.
在女性,缺铁性贫血的最常见原因是多次怀孕,月经次数过多,因妇科病原产生的
月经过多.在这些情况必须用口服抗贫血药物来恢复血清和组织内铁浓度(1).
铁剂有二价铁无机盐,有机盐和铁蛋白.这些铁剂的吸收度各不同,是因其化学结
构,跟餐服用时间及贫血严重性而定.
二价铁无机盐的吸收比其他铁剂迅速及完全,但局限于常出现的副反应如腹泻,便
秘,恶心,呕吐及心口灼热,这些副反应是因铁离子直接刺激胃粘膜(2).
铁蛋白络合物有较好的耐受性,此测试评价了蛋白琥珀酸铁(*)跟铁蛋白用于缺铁性
贫血在妇产科的住院病人的疗效及耐受性.
蛋白琥珀酸铁的特征是:在胃内酸性环境产生沉淀物,不会释放出铁离子,所以不
会产生胃粘膜损害,相反地,在肠内较高的酸碱度,化合物重新变得可溶,胰酶使
它释放出铁离子可供吸收之用(3,4).
此化合物由铁与乳剂琥珀酸蛋白结合,是一个耐受性高的铁剂.
方法
40个女性(年龄由19-52岁;平均年龄:33.32岁±1.54 SE),患有缺铁性贫血.
缺铁性贫血的原因为怀孕3个月(6个病例),产后出血(7个病例),流产或危迫流产(8
个病例),胎盘脱落后出血(1个病例)或良性妇科病原(停经时子宫出血6例;子宫纤
维病3例;月经次数过多3例;子宫颈息肉病5例;子宫内膜组织异位1例).
在所有有妇科病原的病例,在测试前会先以药物或手术停止出血来治疗贫血的病因.
产科缺铁性贫血病例血清血红蛋白浓度(Hb)的幅度如下:
- 怀孕12至16周;Hb:15.9g/100ml
- 怀孕17至24周;Hb:10.9g/100ml
- 怀孕25至40周及产子;Hb:10.3g/100ml
妇科缺铁性贫血病例血清血红蛋白浓度(Hb)的幅度为8至11.5/100ml.
所有病因引起的缺铁性贫血的血清铁浓度均低于65μg/100ml.
患有因不明病因,赘瘤,持续性出血,严重肠胃,肝和肾病而产生的缺铁性贫血病
例并没有被列入此测试中.
病例被随机地分为两组,每组20个病例,一组口服蛋白琥珀酸铁(每天2次,每次一
瓶相等于40mg三价铁),另一组口服铁蛋白微粒化胶囊(每天2次,每次1粒相等于
40mg三价铁),药物均为餐前服用,疗程为40天.
其他可影响造血或铁吸收的药物如制酸剂或维生素C在测试时禁用.
在疗程开始时,20天后及结束时,记录以下血化学参数以评价两种药品的疗效:Hb,
红血球数RBC,红细胞压积(Ht),平均细胞容量(MCV),平均细胞血红蛋白(MCH),
平均细胞血红蛋白浓度(MCHC)及血清铁浓度,在以上观察时间也记录了以下临床
参数:乏力,神情呆滞,皮肤及粘膜苍白和易疲性,以0(=不存在)至3(=严重)的标
准来评价其程度.
在以上三个观察时间也记录可能出现的副反应(种类,为期,严重性和跟药物的关系)
及一些血液和临床参数的变化(ESR,白血球数WBC,血小板数,血压及心率)来评
价药物的耐受性.
疗程结束后,医生及病人也对两种药物的疗效及耐受性作出总评价.
统计学上以非参数Wilcoxon's检验来比较每组的资料及非参数Mann-Whitney's
U-检验比较两个疗程的差别.
结果及结论
铁蛋白组中:有1个病例在第33天终止疗程因对铁蛋白的耐受性差(她出现为期10天
中度恶心和心口灼热及为期5天的严重腹泻);另1病例在怀孕38周及疗程20天后因
接受剖腹产子手术而终止疗程.
表I和II列出蛋白琥珀酸铁组及铁蛋白组在3个观察时间的血液参数.
表III列出在疗程前及后,以统计学分析两组疗程数据的比较.
疗程开始时,两组大部分血液参数(Ht和MCH除外)是均一性的.
30天后,不论是蛋白琥珀酸铁组或铁蛋白组的病例在几乎所有血液参数均有好转.
蛋白琥珀酸铁组Hb,RBC及MCH的上升很明显地比铁蛋白组为高(图1).
蛋白琥珀酸铁也有优良的临床结果.
治疗前,蛋白琥珀酸铁组有4个病例有神情呆滞,接受治疗后20天即消失.治疗前,
铁蛋白组有5个病例有此症状,只有4个病例得到改善,但此症状依然持续.
治疗前,所有病例均有皮肤苍白.20天后,蛋白琥珀酸铁组有7个病例此症状消失
了,13个病例得到好转;而在对照组只有3个病例此症状消失了及17个病例得到好
转.疗程结束时,蛋白琥珀酸铁组中此症状只在1个病例持续,而铁蛋白组仍有11
个病例有此症状.在此方面,蛋白琥珀酸铁明显地优胜于铁蛋白(图2).
疗程开始时,蛋白琥珀酸铁组有13个病例,对照组有17个病例有粘膜苍白.20天后,
蛋白琥珀酸铁组只有2个病例仍有此症状而对照组即有6个病例.疗程结束时,此症
状在蛋白琥珀酸铁组1个病例持续及铁蛋白组5个病例持续.
疗程开始时,蛋白琥珀酸铁组有15个病例,铁蛋白组有12个病例有易疲性.20天后,
此症状在蛋白琥珀酸铁组中12个病例消失而在铁蛋白组中只5个病例消失.疗程结
束时,此症状在蛋白琥珀酸铁组1个病例持续及对照组7个病例持续.
在此方面,蛋白琥珀酸铁明显地优胜于铁蛋白(图3).
疗效的评价如下:
蛋白琥珀酸铁 铁蛋白
医生 病人 医生 病人
很好 10 8 1 0
好 10 12 16 14
差 0 0 1 4
没评价 0 0 2 2
Chi-square检验证实在医生(Chi-square:11.74;P<0.01)及病人(Chi-square,
14.15;P<0.01)评价中,蛋白琥珀酸铁很明显地比铁蛋白为佳.
用于分析系统性耐受性的生物参数并没有重要的变化.
两组病人顺从性都好.铁蛋白组有1个病例出现严重胃副反应,疗程因而被终止.
蛋白琥珀酸铁组有1个病例出现轻微腹泻,此症状为期4天而不需以药物治疗.
总结来说,在妇产科应用时,蛋白琥珀酸铁比铁蛋白更迅速及有效地治疗缺铁性贫
血,血液参数的上升亦比铁蛋白更明显及更高.
蛋白琥珀酸铁的耐受性非常好,解决了在一般铁剂因副反映的局限性.
(*) 蛋白琥珀酸铁,意大利意大泛马克大药厂专利产品,产品名菲普利
图 1
平均血清血红蛋白数值
12
蛋白琥珀酸铁
对照品
11
10
9
治疗开始时 治疗20天 治疗40天
图 2
皮肤苍白的平均数值
3
蛋白琥珀酸铁
对照品
2
1
0
治疗开始时 治疗20天 治疗40天
图 3
易疲性的平均数值
3
蛋白琥珀酸铁
对照品
2
1
0
治疗开始时 治疗20天 治疗40天
表 I – 蛋白琥珀酸铁组在不同观察时间 ( T0 = 治疗开始时; T20 = 20天,
T40 = 40天)血液参数(平均±SE)及症状的严重性(平均±SE).
参数 T0 T20 T40
Wilcoxon's 检验
1= T0 vs. T20
2= T20 vs. T40
Ht(%) 37.93±0.69 38.35±0.6238.55±0.72
1= N.S.
2= P<0.05
Hb(g/100ml) 10.40±0.11 10.98±0.1311.71±0.14
1= P<0.01
2= P<0.01
RBC(×10
6
/mm
3
) 4.10±0.09 4.22±0.09 4.32±0.09
1= P<0.01
2= P<0.01
MCV(
3
) 83.62±0.99 84.77±1.0785.61±1.10
1= P<0.01
2= P<0.01
MCH(pg) 24.94±0.42 25.70±0.4126.38±0.47
1= P<0.01
2= P<0.01
MCHC(g/100ml) 28.84±0.44 29.34±0.4330.37±0.49
1= N.S
2= P<0.01
血清铁
( g/100ml)
60.15±2.60 63.90±2.3267.70±2.09
1= P<0.01
2= P<0.01
皮肤苍白 1.70±0.13 0.75±0.14 0.05±0.05
1= P<0.01
2= P<0.01
粘膜苍白 1.08±0.08 0.15±0.10 0.08±0.08
1= P<0.01
2= P<0.01
易疲性 1.13±0.09 0.20±0.11 0.07±0.07
1= P<0.01
2= P<0.01
(*)N.S. = 不明显
表 II – 铁蛋白组在不同观察时间(T0 = 治疗开始时; T20 = 20天,
T40 = 40天)血液参数(平均±SE)及症状的严重性(平均±SE).
参数 T0 T20 T40
Wilcoxon's 检验
1= T0 vs. T20
2= T20 vs. T40
Ht(%) 40.45±0.55 40.83±0.56 41.24±0.52
1= N.S.
2= P<0.05
Hb(g/100ml) 10.27±0.12 10.71±0.15 10.99±0.18
1= P<0.01
2= P<0.01
RBC(×106/mm3) 4.13±0.10 4.19±0.10 4.20±0.09
1= P<0.01
2= P<0.01
MCV( 3) 84.50±1.13 85.50±1.00 85.89±1.00
1= P<0.01
2= P<0.01
MCH(pg) 26.12±0.35 26.53±0.35 26.96±0.44
1= P<0.01
2= P<0.01
MCHC(g/100ml) 29.82±0.30 30.37±0.30 30.75±0.38
1= N.S
2= P<0.01
血清铁
( g/100ml)
58.45±2.77 62.15±2.74 65.10±2.94
1= P<0.01
2= P<0.01
皮肤苍白 1.65±0.11 1.10±0.14 0.55±0.11
1= P<0.01
2= P<0.01
粘膜苍白 1.06±0.06 0.41±0.15 0.35±0.15
1= P<0.01
2= P<0.01
易疲性 1.33±0.14 0.83±0.24 0.75±0.22
1= P<0.01
2= P<0.01
(*)N.S. = 不明显
表 III – 使用统计学Mann-Whitney's U-检验来比较两组疗程.
参数 开始时数值的均一性
两组跟开始时数值的差别
作出比较
Ht(%) P<0.01 N.S.
Hb(g/100ml) N.S. P<0.01
RBC(×10
6
/mm
3
) N.S. P<0.01
MCV(
3
) N.S. N.S.
MCH(pg) P<0.05 P<0.05
MCHC(g/100ml) N.S. N.S.
血清铁
( g/100ml)
N.S. N.S.
皮肤苍白 N.S. P<0.01
粘膜苍白 N.S. N.S.
易疲性 N.S. P<0.05
(*)N.S. = 不明显
IRON PROTEINSUCCINYLATE IN THE TREATMENT OF IRON DEFICIENCY IN
OBSTETRICS AND GYNECOLOGY.
R. Bracchitta and G. Santoni
(Obstetric and Gynecology Dept., Head Physician; G. Santoni,
Hospital "Predabissi" Melegnano, Milan, Italy).
SUMMARY
Forty patients suffering from iron deficiency anemia from obstetrical or
gynecological etiology were randomly treated with iron proteinsuccinylate or
microencapsulated ferritin, at the daily doses of 80 mg Fe
3+
, for 40 days.
Both drugs induced a statistically significant improvement in all the initially
compromised hematological parameters but better results were obtained with
iron proteinsuccinylate in some hematological (serum hemoglobin
concentration and RBC count) and clinical (pallor and fatigability) variables.
One severe case of gastrointestinal intolerance requiring treatment withdrawal
occurred during ferritin treatment, but only one case of mild diarrhea was
reported during iron proteinsuccinylate treatment.
In all other patients, treatments were well tolerated.
INTRODUCTION
Iron is an element essential for hemoglobin synthesis.
In the human body, the progressive reduction in iron reserves causes different
clinical pictures ranging from latent to overt anemia: sometimes, iron
deficiency anemia occurs during growth due to either insufficient dietary
intake or gastrointestinal disturbancies.
More often in women, chronic hemorrhages due to hyper-menorrhea, abortion
or childbirth cause iron deficiency, since the common diet does not supply the
augmented iron requirement.
Normally in the body, iron is not consumed or wasted but totally reused by
endoplasmic reticulum for the hemopoietic system; therefore, the reason for a
negative iron balance is mostly due to the lost iron amount greater than the
absorbed.
Iron deficiency anemia is the most frequent anemia; in fact, it occurs in a great
percentage of fertile (20-30%) and pregnant (15-58%) women.
The most common causes of iron deficiency anemia in women are frequent
pregnancies, poly-menorrhea, or metrorrhagia due to different gynecological
pathologies; in these conditions, serum and tissue iron concentration must be
restored by means of oral antianemic drugs (1).
Iron may be administered as ferrous inorganic salts, organic salts or extractive
ferritin. The absorption of these derivatives is different and depends on their
chemical structure, on the meal-related administration time and on the severity
of the anemia.
Ferrous inorganic salts are absorbed more quickly and completely than other
compounds but their use is limited by the high occurrence of side effects,
such as diarrhea, constipation, nausea, vomiting and heartburn, which are
caused by the direct irritating action of iron ions on the gastrointestinal
mucosa (2).
Formulations which contain iron bound in a proteic complex show better
tolerability; among these, we assessed the efficacy and tolerability of iron
proteinsuccinylate (*) vs. an extractive ferritin in patients affected with iron
deficiency anemia and hospitalized in an Obstetrics and Gynecology
department.
Iron proteinsuccinylate has a particular behavior: in the stomach, due to the
acidic pH, it precipitates in fair number of clots from which iron ions cannot be
released so that gastric mucosa damage does not occur. On the contrary, in
the intestines, because of the increase of the pH, the compound redissolves
and the consequent attack by pancreatic enzymes separates the iron from the
complex and makes it available for absorption (3, 4).
This compound formed by adding iron to succinylated milk proteins mainly
casein, may be considered as a harmless and well tolerated iron "carrier".
(*) ITF 282, patented by Italfarmaco S.p.A (Italy)
CAS No.93615-44-2
Trademark: FERPLEX - Lifepharma S.p.A. (Italy)
MATERIALS AND METHODS
Forty women (aged between 19 and 52 years: mean age: 33.32 yrs ± 1.54 S.E.
suffering from iron deficiency anemia were admitted to the trial.
Iron deficiency was due to pregnancy from the 3
rd
month (6 cases), postpartum
hemorrhage (7 cases), abortion or threatened abortion (8 cases), hemorrhage
following to placenta previa (1 case) or benign gynecological pathologies
( metrorrhagia in menopause; 6 cases; uterine fibroma; 3 cases;
hyperpolymenorrhea; 3 cases; uterine cervix polyposis; 5 cases;
endometriosis; 1 case).
In all patients with gynecological pathologies the cause of anemia was
previously cured with drugs or surgery in order to stop bleeding.
For iron deficiency anemia in obstetrical patients, the admittance limits for
serum hemoglobin concentration (Hb) were as follows;
- pregnancy from 12 to 16 weeks; Hb: 11.5g/100 ml
- pregnancy from 17 to 24 weeks; Hb: 10.9g/100 ml
- pregnancy from 25 to 40 weeks and purperium; Hb: 10.3g/100 ml
For iron deficiency anemia due to gynecological causes, admittances limits of
Hb ranged from 8 to 11.5g/100 ml.
Independently from the origin, iron deficiency anemia had however to be
characterized by serum iron concentration lower than 65 g/100 ml.
Patients suffering from iron deficiency anemia due to unclear pathologies,
neoplasies, persistent bleeding, as well as severe gastrointestinal, hepatic or
renal diseases were excluded from the trial.
Patients were randomly divided into 2 treatment groups of 20 patients each
and treated orally either with iron proteinsuccinylate (one 40 mg Fe
3+
vial/b.i.d.)
or microencapsulated ferritin (one 40mg Fe
3+
capsule/b.i.d.). Treatment was
administered, before meals, for 40 days.
Other therapy, which could interfere with hemopoiesis or iron absorption,
such as antiacid drugs or ascorbic acid, was not permitted during the trial.
The efficacy of both drugs was evaluated by recording, at the beginning, after
20 days and at termination, the following hematochemical parameters; Hb,
RBC count, hematocrit (Ht), mean corpuscular volume (MCV), mean
corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration
(MCHC) and serum iron concentration. At the same observation times, some
clinical parameters such as asthenia, apathy, skin and mucosa pallor and
fatigability were recorded as well; their intensity was judged by means of a
score scale ranging from 0 (= absent) to 3 (= severe).
Possible side effects (their type, duration, severity and relationship with
treatments) and every variation of some hematological and clinical parameters
(ESR, WBC count, platelet count, blood pressure and cardiac rate), were
carefully checked and recorded at the 3 observation times in order to assess
the drug tolerability.
At the end of treatment, an overall judgment of the efficacy and tolerability of
both drugs was expressed by physicians and patients.
Statistical evaluation was made by using the nonparametric Wilcoxon's test
for comparisons within groups and the nonparametric Mann-Whitney's U-test
for comparisons between treatments.
RESULTS AND DISCUSSION
One patient withdrew from treatment at day 33 because of intolerance to
ferritin (she complained of moderate nausea and heartburn, that lasted 10 days
and of severs diarrhea that lasted 5 days); a second woman, at the 38
th
week of
pregnancy, stopped the treatment with the reference drug after 20 days of
treatment because of cesarean surgery.
The values, recorded at the 3 observation times, of the hematological
parameters of patients treated either with iron proteinsuccinylate or ferritin are
reported in Tables I and II, respectively.
Table III shows the results of the statistical analysis made to compare the
values between the two treatment groups before and after treatment.
At the beginning, most of the hematological parameters, except Ht and MCH,
were homogeneous between the two treatment groups.
In patients treated with iron proteinsuccinylate or ferritin, marked
improvements of the hematological parameters were observed in almost all
the considered parameters already after 30 days.
The comparison between the two treatments proved that the increases in Hb
(Figure 1), RBC count and MCH were more marked in the patients treated with
iron proteinsuccinylate than with ferritin and the statistical differences
between treatments were highly significant.
Excellent clinical results were obtained with iron proteinsuccinylate as well.
Apathy, present in 4 patients before iron proteinsuccinylare treatment, abated
already at day 20; this symptom, even if improved, was still present in the 4/5
patients treated with ferritin.
Skin pallor was initially present in all patients; at the middle check, it abated in
7 patients and improved in improved in 13 of the group treated with iron
proteinsuccinylate, while it abated in only 3 patients and improved in 17 of the
reference group. At termination, the symptom persisted only in 1 woman after
iron proteinsuccinylate treatment but in 11 women after ferritin therapy.
Also for this parameter, a high statistical significance in favor of iron
proteinsuccinylate appears from the comparison between the two treatments
(Figure 2).
Mucosa paleness was present at day 20 only in 2 out of 13 women of the test
treatment group and in 6 out of 17 women of the reference group; at
termination, this symptom persisted in 1 case of iron proteinsuccinylate group
and in 5 patients of the ferritin group.
Fatigability, initially experienced by 15 women of the iron proteinsuccinylate
group and in 12 women of the ferritin group, abated in 12 patients treated with
the test drug and in 5 patients treated with ferritin already at day 20; it was still
present in 1 woman of the iron proteinsuccinylate group and in 7 women of the
reference drug group, at termination.
The statistical difference between groups in the abatement of this symptom
was in favor of iron proteinsuccinylate (Figure 3).
Efficacy was judged as follows:
Iron proteinsuccinylate Ferritin
Physician Patient Physician Patient
excellent 10 8 1 0
good 10 12 16 14
poor 0 0 1 4
nil 0 0 2 2
Chi-square test showed a high statistical significance in favor of iron
proteinsuccinylate both for the physician's judgment (chi-square:11.74; P<0.01)
and the patient's judgment ( chi-square:14.15; P<0.01)
The biological parameters, considered in order to asses the systemic
tolerability, showed no important variations.
Compliance was good in all patients of both groups: one patient complaned of
severe gastric intolerance which caused the interruption of ferritin treatment.
Mild diarrhea, which lasted 4 days and required no medical management,
occurred in one patient treated with iron proteinsuccinylate.
In conclusion, iron proteinsuccinylate appeared more rapid and effective in
treating iron deficiency anemia in obstetrics and gynecology inducing
significant and greater increases in the classical hematological parameters
and improving the parameters more markedly than ferritin.
Furthermore, iron proteinsuccinylate proved to be very well tolerated thus
overcoming this common limit of iron compounds.
REFERENCES
1) Lee G.R., Wintrobe M.M., Bunn H.F.
IRON DEFICIENCY ANEMIA AND THE SIDEROBLASTIC ANEMIAS
Harrison's principles of internal medicine
XI Edizione , New York 1980, pag. 1514
2) Hillman R.S., Finch C.A..
DRUGS EFFECTIVE IN IRON-DEFICIENCY AND OTHER HYPOCHROMIC
ANEMIAS
Goodmand and gilman's - The pharmacological basis of therapeutics
VII Edizone, New York 1985, pag. 1308
3) Cremonesi P. et al.
Iron derivatives of iron modified milk protein
Arzneim. Forsch. Drug Res. 34(II), 9, 952-958, 1984
4) Pagella P.G. et al.
PHARMACOLOGICAL AND TOXICOLOGICAL STUDIES ON AN IRON
SUCCINYLPROTEIN COMPLEX (ITF 182) FOR ORAL TREATMENT OF IRON
DEFICIENCY ANEMIA
Arzneim. Forsch. Drug Res. 34(II), 9, 952-958, 1984
FIGURE 1
MEAN VALUES OF SERUM HEMOGLOBIN
12
ITF282
CONTROL
11
10
9
AT DAY 0 AT DAY 20 AT DAY 40
FIGURE 2
MEAN SCORE VALUES OF SKIN PALLOR
3
ITF282
CONTROL
2
1
0
AT DAY 0 AT DAY 20 AT DAY 40
FIGURE 3
MEAN SCORE VALUES OF FATIGABILITY
3
ITF282
CONTROL
2
1
0
AT DAY 0 AT DAY 20 AT DAY 40
TABLE I - Values of the hematological parameters (mean ± S. E.) and severity
scores assigned to the considered symptoms (mean ± S. E) of patients treated
with iron proteinsuccinylate, at various observation times ( T0 = at day 0; T20 =
at day 20 and T40 = at day 40).
VARIABLES T0 T20 T40
Wilcoxon's test
1= T0 vs. T20
2= T20 vs. T40
Ht(%) 37.93±0.69 38.35±0.6238.55±0.72
1= N.S.
2= P<0.05
Hb(g/100ml) 10.40±0.11 10.98±0.1311.71±0.14
1= P<0.01
2= P<0.01
RBC(×10
6
/mm
3
) 4.10±0.09 4.22±0.09 4.32±0.09
1= P<0.01
2= P<0.01
MCV(
3
) 83.62±0.99 84.77±1.0785.61±1.10
1= P<0.01
2= P<0.01
MCH(pg) 24.94±0.42 25.70±0.4126.38±0.47
1= P<0.01
2= P<0.01
MCHC(g/100ml) 28.84±0.44 29.34±0.4330.37±0.49
1= N.S
2= P<0.01
Serum iron
( g/100ml)
60.15±2.60 63.90±2.3267.70±2.09
1= P<0.01
2= P<0.01
Skin pallor 1.70±0.13 0.75±0.14 0.05±0.05
1= P<0.01
2= P<0.01
Mucosa pallor 1.08±0.08 0.15±0.10 0.08±0.08
1= P<0.01
2= P<0.01
Fatigability 1.13±0.09 0.20±0.11 0.07±0.07
1= P<0.01
2= P<0.01
(*)N.S. = NOT SIGNIFCANT
TABLE II - Values of the hematological parameters (mean ± S. E.) and severity
s cores assigned to the considered symptoms (mean ± S. E) in patients treated
with extractive ferritin, at various observation times ( T0 = at day 0; T20 = at day
20 and T40 = at day 40).
VARIABLES T0 T20 T40
Wilcoxon's test
1= T0 vs. T20
2= T20 vs. T40
Ht(%) 40.45±0.55 40.83±0.56 41.24±0.52
1= N.S.
2= P<0.05
Hb(g/100ml) 10.27±0.12 10.71±0.15 10.99±0.18
1= P<0.01
2= P<0.01
RBC(×106/mm3) 4.13±0.10 4.19±0.10 4.20±0.09
1= P<0.01
2= P<0.01
MCV( 3) 84.50±1.13 85.50±1.00 85.89±1.00
1= P<0.01
2= P<0.01
MCH(pg) 26.12±0.35 26.53±0.35 26.96±0.44
1= P<0.01
2= P<0.01
MCHC(g/100ml) 29.82±0.30 30.37±0.30 30.75±0.38
1= N.S
2= P<0.01
Serum iron
( g/100ml)
58.45±2.77 62.15±2.74 65.10±2.94
1= P<0.01
2= P<0.01
Skin pallor 1.65±0.11 1.10±0.14 0.55±0.11
1= P<0.01
2= P<0.01
Mucosa pallor 1.06±0.06 0.41±0.15 0.35±0.15
1= P<0.01
2= P<0.01
Fatigability 1.33±0.14 0.83±0.24 0.75±0.22
1= P<0.01
2= P<0.01
(*)N.S. = NOT SIGNIFCANT
TABLE III - Results of the statistical analysis carried out by means of
Mann-Whitney's U test for comparisons between treatments.
VARIABLES
Homogeneity of initial
values
Comparison on the differences vs.
initial values
Ht(%) P<0.01 N.S.
Hb(g/100ml) N.S. P<0.01
RBC(×10
6
/mm
3
) N.S. P<0.01
MCV(
3
) N.S. N.S.
MCH(pg) P<0.05 P<0.05
MCHC(g/100ml) N.S. N.S.
Serum iron
( g/100ml)
N.S. N.S.
Skin pallor N.S. P<0.01
Mucosa pallor N.S. N.S.
Fatigability N.S. P<0.05
(*)N.S. = NOT SIGNIFCANT
99880
·上一篇：缺铁性贫血病程中反复!次大便潜血检查阴性胃镜检
·下一篇：儿童营养性缺铁性贫血铁剂治疗效果观察
Bracchitta R. & Santoni G.
意大利,米兰 Predabissi 医院,妇产科
Boll. Chim. Farm., Suppl: Clinica e. Terapia. Anno 127, No., 3, 3/1998
简介
40例患有缺铁性贫血的妇产科病人,随机性地使用蛋白琥珀酸铁或铁蛋白作治疗,
每天剂量为80毫克三价铁,疗程为40天.
两种药物都对血液参数有所提升,但蛋白琥珀酸铁的效果比较好,尤其是血清血红
蛋白浓度,红血球数量及在治疗脸色苍白及易疲性方面.
其中一例,服用铁蛋白的病人因产生严重胃肠副作用要退出此测试;而服用蛋白琥
珀酸铁组,只有一个病例产生轻微腹泻.
所有病例耐受性都很好.
介绍
铁是血红蛋白合成的必要元素.
人体内持续性的铁储存量减少会产生相对性至绝对性贫血,缺铁性贫血可因发育时
在饮食吸收率不足或肠胃疾病而产生.
女性经常因月经过多,流产或生育产生慢性出血而引至缺铁性贫血.饮食中的铁质
不足以满足体内需求.
一般在体内,铁质不会被消耗而只会在内质网小胞体被循环作造血系统之用,所以
缺铁一般是因铁流失量超于吸收量所致.
缺铁性贫血是最普遍的贫血,在育龄女性发生率为20-30%,在孕妇发生率为15-58%.
在女性,缺铁性贫血的最常见原因是多次怀孕,月经次数过多,因妇科病原产生的
月经过多.在这些情况必须用口服抗贫血药物来恢复血清和组织内铁浓度(1).
铁剂有二价铁无机盐,有机盐和铁蛋白.这些铁剂的吸收度各不同,是因其化学结
构,跟餐服用时间及贫血严重性而定.
二价铁无机盐的吸收比其他铁剂迅速及完全,但局限于常出现的副反应如腹泻,便
秘,恶心,呕吐及心口灼热,这些副反应是因铁离子直接刺激胃粘膜(2).
铁蛋白络合物有较好的耐受性,此测试评价了蛋白琥珀酸铁(*)跟铁蛋白用于缺铁性
贫血在妇产科的住院病人的疗效及耐受性.
蛋白琥珀酸铁的特征是:在胃内酸性环境产生沉淀物,不会释放出铁离子,所以不
会产生胃粘膜损害,相反地,在肠内较高的酸碱度,化合物重新变得可溶,胰酶使
它释放出铁离子可供吸收之用(3,4).
此化合物由铁与乳剂琥珀酸蛋白结合,是一个耐受性高的铁剂.
方法
40个女性(年龄由19-52岁;平均年龄:33.32岁±1.54 SE),患有缺铁性贫血.
缺铁性贫血的原因为怀孕3个月(6个病例),产后出血(7个病例),流产或危迫流产(8
个病例),胎盘脱落后出血(1个病例)或良性妇科病原(停经时子宫出血6例;子宫纤
维病3例;月经次数过多3例;子宫颈息肉病5例;子宫内膜组织异位1例).
在所有有妇科病原的病例,在测试前会先以药物或手术停止出血来治疗贫血的病因.
产科缺铁性贫血病例血清血红蛋白浓度(Hb)的幅度如下:
- 怀孕12至16周;Hb:15.9g/100ml
- 怀孕17至24周;Hb:10.9g/100ml
- 怀孕25至40周及产子;Hb:10.3g/100ml
妇科缺铁性贫血病例血清血红蛋白浓度(Hb)的幅度为8至11.5/100ml.
所有病因引起的缺铁性贫血的血清铁浓度均低于65μg/100ml.
患有因不明病因,赘瘤,持续性出血,严重肠胃,肝和肾病而产生的缺铁性贫血病
例并没有被列入此测试中.
病例被随机地分为两组,每组20个病例,一组口服蛋白琥珀酸铁(每天2次,每次一
瓶相等于40mg三价铁),另一组口服铁蛋白微粒化胶囊(每天2次,每次1粒相等于
40mg三价铁),药物均为餐前服用,疗程为40天.
其他可影响造血或铁吸收的药物如制酸剂或维生素C在测试时禁用.
在疗程开始时,20天后及结束时,记录以下血化学参数以评价两种药品的疗效:Hb,
红血球数RBC,红细胞压积(Ht),平均细胞容量(MCV),平均细胞血红蛋白(MCH),
平均细胞血红蛋白浓度(MCHC)及血清铁浓度,在以上观察时间也记录了以下临床
参数:乏力,神情呆滞,皮肤及粘膜苍白和易疲性,以0(=不存在)至3(=严重)的标
准来评价其程度.
在以上三个观察时间也记录可能出现的副反应(种类,为期,严重性和跟药物的关系)
及一些血液和临床参数的变化(ESR,白血球数WBC,血小板数,血压及心率)来评
价药物的耐受性.
疗程结束后,医生及病人也对两种药物的疗效及耐受性作出总评价.
统计学上以非参数Wilcoxon's检验来比较每组的资料及非参数Mann-Whitney's
U-检验比较两个疗程的差别.
结果及结论
铁蛋白组中:有1个病例在第33天终止疗程因对铁蛋白的耐受性差(她出现为期10天
中度恶心和心口灼热及为期5天的严重腹泻);另1病例在怀孕38周及疗程20天后因
接受剖腹产子手术而终止疗程.
表I和II列出蛋白琥珀酸铁组及铁蛋白组在3个观察时间的血液参数.
表III列出在疗程前及后,以统计学分析两组疗程数据的比较.
疗程开始时,两组大部分血液参数(Ht和MCH除外)是均一性的.
30天后,不论是蛋白琥珀酸铁组或铁蛋白组的病例在几乎所有血液参数均有好转.
蛋白琥珀酸铁组Hb,RBC及MCH的上升很明显地比铁蛋白组为高(图1).
蛋白琥珀酸铁也有优良的临床结果.
治疗前,蛋白琥珀酸铁组有4个病例有神情呆滞,接受治疗后20天即消失.治疗前,
铁蛋白组有5个病例有此症状,只有4个病例得到改善,但此症状依然持续.
治疗前,所有病例均有皮肤苍白.20天后,蛋白琥珀酸铁组有7个病例此症状消失
了,13个病例得到好转;而在对照组只有3个病例此症状消失了及17个病例得到好
转.疗程结束时,蛋白琥珀酸铁组中此症状只在1个病例持续,而铁蛋白组仍有11
个病例有此症状.在此方面,蛋白琥珀酸铁明显地优胜于铁蛋白(图2).
疗程开始时,蛋白琥珀酸铁组有13个病例,对照组有17个病例有粘膜苍白.20天后,
蛋白琥珀酸铁组只有2个病例仍有此症状而对照组即有6个病例.疗程结束时,此症
状在蛋白琥珀酸铁组1个病例持续及铁蛋白组5个病例持续.
疗程开始时,蛋白琥珀酸铁组有15个病例,铁蛋白组有12个病例有易疲性.20天后,
此症状在蛋白琥珀酸铁组中12个病例消失而在铁蛋白组中只5个病例消失.疗程结
束时,此症状在蛋白琥珀酸铁组1个病例持续及对照组7个病例持续.
在此方面,蛋白琥珀酸铁明显地优胜于铁蛋白(图3).
疗效的评价如下:
蛋白琥珀酸铁 铁蛋白
医生 病人 医生 病人
很好 10 8 1 0
好 10 12 16 14
差 0 0 1 4
没评价 0 0 2 2
Chi-square检验证实在医生(Chi-square:11.74;P<0.01)及病人(Chi-square,
14.15;P<0.01)评价中,蛋白琥珀酸铁很明显地比铁蛋白为佳.
用于分析系统性耐受性的生物参数并没有重要的变化.
两组病人顺从性都好.铁蛋白组有1个病例出现严重胃副反应,疗程因而被终止.
蛋白琥珀酸铁组有1个病例出现轻微腹泻,此症状为期4天而不需以药物治疗.
总结来说,在妇产科应用时,蛋白琥珀酸铁比铁蛋白更迅速及有效地治疗缺铁性贫
血,血液参数的上升亦比铁蛋白更明显及更高.
蛋白琥珀酸铁的耐受性非常好,解决了在一般铁剂因副反映的局限性.
(*) 蛋白琥珀酸铁,意大利意大泛马克大药厂专利产品,产品名菲普利
图 1
平均血清血红蛋白数值
12
蛋白琥珀酸铁
对照品
11
10
9
治疗开始时 治疗20天 治疗40天
图 2
皮肤苍白的平均数值
3
蛋白琥珀酸铁
对照品
2
1
0
治疗开始时 治疗20天 治疗40天
图 3
易疲性的平均数值
3
蛋白琥珀酸铁
对照品
2
1
0
治疗开始时 治疗20天 治疗40天
表 I – 蛋白琥珀酸铁组在不同观察时间 ( T0 = 治疗开始时; T20 = 20天,
T40 = 40天)血液参数(平均±SE)及症状的严重性(平均±SE).
参数 T0 T20 T40
Wilcoxon's 检验
1= T0 vs. T20
2= T20 vs. T40
Ht(%) 37.93±0.69 38.35±0.6238.55±0.72
1= N.S.
2= P<0.05
Hb(g/100ml) 10.40±0.11 10.98±0.1311.71±0.14
1= P<0.01
2= P<0.01
RBC(×10
6
/mm
3
) 4.10±0.09 4.22±0.09 4.32±0.09
1= P<0.01
2= P<0.01
MCV(
3
) 83.62±0.99 84.77±1.0785.61±1.10
1= P<0.01
2= P<0.01
MCH(pg) 24.94±0.42 25.70±0.4126.38±0.47
1= P<0.01
2= P<0.01
MCHC(g/100ml) 28.84±0.44 29.34±0.4330.37±0.49
1= N.S
2= P<0.01
血清铁
( g/100ml)
60.15±2.60 63.90±2.3267.70±2.09
1= P<0.01
2= P<0.01
皮肤苍白 1.70±0.13 0.75±0.14 0.05±0.05
1= P<0.01
2= P<0.01
粘膜苍白 1.08±0.08 0.15±0.10 0.08±0.08
1= P<0.01
2= P<0.01
易疲性 1.13±0.09 0.20±0.11 0.07±0.07
1= P<0.01
2= P<0.01
(*)N.S. = 不明显
表 II – 铁蛋白组在不同观察时间(T0 = 治疗开始时; T20 = 20天,
T40 = 40天)血液参数(平均±SE)及症状的严重性(平均±SE).
参数 T0 T20 T40
Wilcoxon's 检验
1= T0 vs. T20
2= T20 vs. T40
Ht(%) 40.45±0.55 40.83±0.56 41.24±0.52
1= N.S.
2= P<0.05
Hb(g/100ml) 10.27±0.12 10.71±0.15 10.99±0.18
1= P<0.01
2= P<0.01
RBC(×106/mm3) 4.13±0.10 4.19±0.10 4.20±0.09
1= P<0.01
2= P<0.01
MCV( 3) 84.50±1.13 85.50±1.00 85.89±1.00
1= P<0.01
2= P<0.01
MCH(pg) 26.12±0.35 26.53±0.35 26.96±0.44
1= P<0.01
2= P<0.01
MCHC(g/100ml) 29.82±0.30 30.37±0.30 30.75±0.38
1= N.S
2= P<0.01
血清铁
( g/100ml)
58.45±2.77 62.15±2.74 65.10±2.94
1= P<0.01
2= P<0.01
皮肤苍白 1.65±0.11 1.10±0.14 0.55±0.11
1= P<0.01
2= P<0.01
粘膜苍白 1.06±0.06 0.41±0.15 0.35±0.15
1= P<0.01
2= P<0.01
易疲性 1.33±0.14 0.83±0.24 0.75±0.22
1= P<0.01
2= P<0.01
(*)N.S. = 不明显
表 III – 使用统计学Mann-Whitney's U-检验来比较两组疗程.
参数 开始时数值的均一性
两组跟开始时数值的差别
作出比较
Ht(%) P<0.01 N.S.
Hb(g/100ml) N.S. P<0.01
RBC(×10
6
/mm
3
) N.S. P<0.01
MCV(
3
) N.S. N.S.
MCH(pg) P<0.05 P<0.05
MCHC(g/100ml) N.S. N.S.
血清铁
( g/100ml)
N.S. N.S.
皮肤苍白 N.S. P<0.01
粘膜苍白 N.S. N.S.
易疲性 N.S. P<0.05
(*)N.S. = 不明显
IRON PROTEINSUCCINYLATE IN THE TREATMENT OF IRON DEFICIENCY IN
OBSTETRICS AND GYNECOLOGY.
R. Bracchitta and G. Santoni
(Obstetric and Gynecology Dept., Head Physician; G. Santoni,
Hospital "Predabissi" Melegnano, Milan, Italy).
SUMMARY
Forty patients suffering from iron deficiency anemia from obstetrical or
gynecological etiology were randomly treated with iron proteinsuccinylate or
microencapsulated ferritin, at the daily doses of 80 mg Fe
3+
, for 40 days.
Both drugs induced a statistically significant improvement in all the initially
compromised hematological parameters but better results were obtained with
iron proteinsuccinylate in some hematological (serum hemoglobin
concentration and RBC count) and clinical (pallor and fatigability) variables.
One severe case of gastrointestinal intolerance requiring treatment withdrawal
occurred during ferritin treatment, but only one case of mild diarrhea was
reported during iron proteinsuccinylate treatment.
In all other patients, treatments were well tolerated.
INTRODUCTION
Iron is an element essential for hemoglobin synthesis.
In the human body, the progressive reduction in iron reserves causes different
clinical pictures ranging from latent to overt anemia: sometimes, iron
deficiency anemia occurs during growth due to either insufficient dietary
intake or gastrointestinal disturbancies.
More often in women, chronic hemorrhages due to hyper-menorrhea, abortion
or childbirth cause iron deficiency, since the common diet does not supply the
augmented iron requirement.
Normally in the body, iron is not consumed or wasted but totally reused by
endoplasmic reticulum for the hemopoietic system; therefore, the reason for a
negative iron balance is mostly due to the lost iron amount greater than the
absorbed.
Iron deficiency anemia is the most frequent anemia; in fact, it occurs in a great
percentage of fertile (20-30%) and pregnant (15-58%) women.
The most common causes of iron deficiency anemia in women are frequent
pregnancies, poly-menorrhea, or metrorrhagia due to different gynecological
pathologies; in these conditions, serum and tissue iron concentration must be
restored by means of oral antianemic drugs (1).
Iron may be administered as ferrous inorganic salts, organic salts or extractive
ferritin. The absorption of these derivatives is different and depends on their
chemical structure, on the meal-related administration time and on the severity
of the anemia.
Ferrous inorganic salts are absorbed more quickly and completely than other
compounds but their use is limited by the high occurrence of side effects,
such as diarrhea, constipation, nausea, vomiting and heartburn, which are
caused by the direct irritating action of iron ions on the gastrointestinal
mucosa (2).
Formulations which contain iron bound in a proteic complex show better
tolerability; among these, we assessed the efficacy and tolerability of iron
proteinsuccinylate (*) vs. an extractive ferritin in patients affected with iron
deficiency anemia and hospitalized in an Obstetrics and Gynecology
department.
Iron proteinsuccinylate has a particular behavior: in the stomach, due to the
acidic pH, it precipitates in fair number of clots from which iron ions cannot be
released so that gastric mucosa damage does not occur. On the contrary, in
the intestines, because of the increase of the pH, the compound redissolves
and the consequent attack by pancreatic enzymes separates the iron from the
complex and makes it available for absorption (3, 4).
This compound formed by adding iron to succinylated milk proteins mainly
casein, may be considered as a harmless and well tolerated iron "carrier".
(*) ITF 282, patented by Italfarmaco S.p.A (Italy)
CAS No.93615-44-2
Trademark: FERPLEX - Lifepharma S.p.A. (Italy)
MATERIALS AND METHODS
Forty women (aged between 19 and 52 years: mean age: 33.32 yrs ± 1.54 S.E.
suffering from iron deficiency anemia were admitted to the trial.
Iron deficiency was due to pregnancy from the 3
rd
month (6 cases), postpartum
hemorrhage (7 cases), abortion or threatened abortion (8 cases), hemorrhage
following to placenta previa (1 case) or benign gynecological pathologies
( metrorrhagia in menopause; 6 cases; uterine fibroma; 3 cases;
hyperpolymenorrhea; 3 cases; uterine cervix polyposis; 5 cases;
endometriosis; 1 case).
In all patients with gynecological pathologies the cause of anemia was
previously cured with drugs or surgery in order to stop bleeding.
For iron deficiency anemia in obstetrical patients, the admittance limits for
serum hemoglobin concentration (Hb) were as follows;
- pregnancy from 12 to 16 weeks; Hb: 11.5g/100 ml
- pregnancy from 17 to 24 weeks; Hb: 10.9g/100 ml
- pregnancy from 25 to 40 weeks and purperium; Hb: 10.3g/100 ml
For iron deficiency anemia due to gynecological causes, admittances limits of
Hb ranged from 8 to 11.5g/100 ml.
Independently from the origin, iron deficiency anemia had however to be
characterized by serum iron concentration lower than 65 g/100 ml.
Patients suffering from iron deficiency anemia due to unclear pathologies,
neoplasies, persistent bleeding, as well as severe gastrointestinal, hepatic or
renal diseases were excluded from the trial.
Patients were randomly divided into 2 treatment groups of 20 patients each
and treated orally either with iron proteinsuccinylate (one 40 mg Fe
3+
vial/b.i.d.)
or microencapsulated ferritin (one 40mg Fe
3+
capsule/b.i.d.). Treatment was
administered, before meals, for 40 days.
Other therapy, which could interfere with hemopoiesis or iron absorption,
such as antiacid drugs or ascorbic acid, was not permitted during the trial.
The efficacy of both drugs was evaluated by recording, at the beginning, after
20 days and at termination, the following hematochemical parameters; Hb,
RBC count, hematocrit (Ht), mean corpuscular volume (MCV), mean
corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration
(MCHC) and serum iron concentration. At the same observation times, some
clinical parameters such as asthenia, apathy, skin and mucosa pallor and
fatigability were recorded as well; their intensity was judged by means of a
score scale ranging from 0 (= absent) to 3 (= severe).
Possible side effects (their type, duration, severity and relationship with
treatments) and every variation of some hematological and clinical parameters
(ESR, WBC count, platelet count, blood pressure and cardiac rate), were
carefully checked and recorded at the 3 observation times in order to assess
the drug tolerability.
At the end of treatment, an overall judgment of the efficacy and tolerability of
both drugs was expressed by physicians and patients.
Statistical evaluation was made by using the nonparametric Wilcoxon's test
for comparisons within groups and the nonparametric Mann-Whitney's U-test
for comparisons between treatments.
RESULTS AND DISCUSSION
One patient withdrew from treatment at day 33 because of intolerance to
ferritin (she complained of moderate nausea and heartburn, that lasted 10 days
and of severs diarrhea that lasted 5 days); a second woman, at the 38
th
week of
pregnancy, stopped the treatment with the reference drug after 20 days of
treatment because of cesarean surgery.
The values, recorded at the 3 observation times, of the hematological
parameters of patients treated either with iron proteinsuccinylate or ferritin are
reported in Tables I and II, respectively.
Table III shows the results of the statistical analysis made to compare the
values between the two treatment groups before and after treatment.
At the beginning, most of the hematological parameters, except Ht and MCH,
were homogeneous between the two treatment groups.
In patients treated with iron proteinsuccinylate or ferritin, marked
improvements of the hematological parameters were observed in almost all
the considered parameters already after 30 days.
The comparison between the two treatments proved that the increases in Hb
(Figure 1), RBC count and MCH were more marked in the patients treated with
iron proteinsuccinylate than with ferritin and the statistical differences
between treatments were highly significant.
Excellent clinical results were obtained with iron proteinsuccinylate as well.
Apathy, present in 4 patients before iron proteinsuccinylare treatment, abated
already at day 20; this symptom, even if improved, was still present in the 4/5
patients treated with ferritin.
Skin pallor was initially present in all patients; at the middle check, it abated in
7 patients and improved in improved in 13 of the group treated with iron
proteinsuccinylate, while it abated in only 3 patients and improved in 17 of the
reference group. At termination, the symptom persisted only in 1 woman after
iron proteinsuccinylate treatment but in 11 women after ferritin therapy.
Also for this parameter, a high statistical significance in favor of iron
proteinsuccinylate appears from the comparison between the two treatments
(Figure 2).
Mucosa paleness was present at day 20 only in 2 out of 13 women of the test
treatment group and in 6 out of 17 women of the reference group; at
termination, this symptom persisted in 1 case of iron proteinsuccinylate group
and in 5 patients of the ferritin group.
Fatigability, initially experienced by 15 women of the iron proteinsuccinylate
group and in 12 women of the ferritin group, abated in 12 patients treated with
the test drug and in 5 patients treated with ferritin already at day 20; it was still
present in 1 woman of the iron proteinsuccinylate group and in 7 women of the
reference drug group, at termination.
The statistical difference between groups in the abatement of this symptom
was in favor of iron proteinsuccinylate (Figure 3).
Efficacy was judged as follows:
Iron proteinsuccinylate Ferritin
Physician Patient Physician Patient
excellent 10 8 1 0
good 10 12 16 14
poor 0 0 1 4
nil 0 0 2 2
Chi-square test showed a high statistical significance in favor of iron
proteinsuccinylate both for the physician's judgment (chi-square:11.74; P<0.01)
and the patient's judgment ( chi-square:14.15; P<0.01)
The biological parameters, considered in order to asses the systemic
tolerability, showed no important variations.
Compliance was good in all patients of both groups: one patient complaned of
severe gastric intolerance which caused the interruption of ferritin treatment.
Mild diarrhea, which lasted 4 days and required no medical management,
occurred in one patient treated with iron proteinsuccinylate.
In conclusion, iron proteinsuccinylate appeared more rapid and effective in
treating iron deficiency anemia in obstetrics and gynecology inducing
significant and greater increases in the classical hematological parameters
and improving the parameters more markedly than ferritin.
Furthermore, iron proteinsuccinylate proved to be very well tolerated thus
overcoming this common limit of iron compounds.
REFERENCES
1) Lee G.R., Wintrobe M.M., Bunn H.F.
IRON DEFICIENCY ANEMIA AND THE SIDEROBLASTIC ANEMIAS
Harrison's principles of internal medicine
XI Edizione , New York 1980, pag. 1514
2) Hillman R.S., Finch C.A..
DRUGS EFFECTIVE IN IRON-DEFICIENCY AND OTHER HYPOCHROMIC
ANEMIAS
Goodmand and gilman's - The pharmacological basis of therapeutics
VII Edizone, New York 1985, pag. 1308
3) Cremonesi P. et al.
Iron derivatives of iron modified milk protein
Arzneim. Forsch. Drug Res. 34(II), 9, 952-958, 1984
4) Pagella P.G. et al.
PHARMACOLOGICAL AND TOXICOLOGICAL STUDIES ON AN IRON
SUCCINYLPROTEIN COMPLEX (ITF 182) FOR ORAL TREATMENT OF IRON
DEFICIENCY ANEMIA
Arzneim. Forsch. Drug Res. 34(II), 9, 952-958, 1984
FIGURE 1
MEAN VALUES OF SERUM HEMOGLOBIN
12
ITF282
CONTROL
11
10
9
AT DAY 0 AT DAY 20 AT DAY 40
FIGURE 2
MEAN SCORE VALUES OF SKIN PALLOR
3
ITF282
CONTROL
2
1
0
AT DAY 0 AT DAY 20 AT DAY 40
FIGURE 3
MEAN SCORE VALUES OF FATIGABILITY
3
ITF282
CONTROL
2
1
0
AT DAY 0 AT DAY 20 AT DAY 40
TABLE I - Values of the hematological parameters (mean ± S. E.) and severity
scores assigned to the considered symptoms (mean ± S. E) of patients treated
with iron proteinsuccinylate, at various observation times ( T0 = at day 0; T20 =
at day 20 and T40 = at day 40).
VARIABLES T0 T20 T40
Wilcoxon's test
1= T0 vs. T20
2= T20 vs. T40
Ht(%) 37.93±0.69 38.35±0.6238.55±0.72
1= N.S.
2= P<0.05
Hb(g/100ml) 10.40±0.11 10.98±0.1311.71±0.14
1= P<0.01
2= P<0.01
RBC(×10
6
/mm
3
) 4.10±0.09 4.22±0.09 4.32±0.09
1= P<0.01
2= P<0.01
MCV(
3
) 83.62±0.99 84.77±1.0785.61±1.10
1= P<0.01
2= P<0.01
MCH(pg) 24.94±0.42 25.70±0.4126.38±0.47
1= P<0.01
2= P<0.01
MCHC(g/100ml) 28.84±0.44 29.34±0.4330.37±0.49
1= N.S
2= P<0.01
Serum iron
( g/100ml)
60.15±2.60 63.90±2.3267.70±2.09
1= P<0.01
2= P<0.01
Skin pallor 1.70±0.13 0.75±0.14 0.05±0.05
1= P<0.01
2= P<0.01
Mucosa pallor 1.08±0.08 0.15±0.10 0.08±0.08
1= P<0.01
2= P<0.01
Fatigability 1.13±0.09 0.20±0.11 0.07±0.07
1= P<0.01
2= P<0.01
(*)N.S. = NOT SIGNIFCANT
TABLE II - Values of the hematological parameters (mean ± S. E.) and severity
s cores assigned to the considered symptoms (mean ± S. E) in patients treated
with extractive ferritin, at various observation times ( T0 = at day 0; T20 = at day
20 and T40 = at day 40).
VARIABLES T0 T20 T40
Wilcoxon's test
1= T0 vs. T20
2= T20 vs. T40
Ht(%) 40.45±0.55 40.83±0.56 41.24±0.52
1= N.S.
2= P<0.05
Hb(g/100ml) 10.27±0.12 10.71±0.15 10.99±0.18
1= P<0.01
2= P<0.01
RBC(×106/mm3) 4.13±0.10 4.19±0.10 4.20±0.09
1= P<0.01
2= P<0.01
MCV( 3) 84.50±1.13 85.50±1.00 85.89±1.00
1= P<0.01
2= P<0.01
MCH(pg) 26.12±0.35 26.53±0.35 26.96±0.44
1= P<0.01
2= P<0.01
MCHC(g/100ml) 29.82±0.30 30.37±0.30 30.75±0.38
1= N.S
2= P<0.01
Serum iron
( g/100ml)
58.45±2.77 62.15±2.74 65.10±2.94
1= P<0.01
2= P<0.01
Skin pallor 1.65±0.11 1.10±0.14 0.55±0.11
1= P<0.01
2= P<0.01
Mucosa pallor 1.06±0.06 0.41±0.15 0.35±0.15
1= P<0.01
2= P<0.01
Fatigability 1.33±0.14 0.83±0.24 0.75±0.22
1= P<0.01
2= P<0.01
(*)N.S. = NOT SIGNIFCANT
TABLE III - Results of the statistical analysis carried out by means of
Mann-Whitney's U test for comparisons between treatments.
VARIABLES
Homogeneity of initial
values
Comparison on the differences vs.
initial values
Ht(%) P<0.01 N.S.
Hb(g/100ml) N.S. P<0.01
RBC(×10
6
/mm
3
) N.S. P<0.01
MCV(
3
) N.S. N.S.
MCH(pg) P<0.05 P<0.05
MCHC(g/100ml) N.S. N.S.
Serum iron
( g/100ml)
N.S. N.S.
Skin pallor N.S. P<0.01
Mucosa pallor N.S. N.S.
Fatigability N.S. P<0.05
(*)N.S. = NOT SIGNIFCANT
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